Pgam5 released from damaged mitochondria induces mitochondrial biogenesis via Wnt signaling

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autorinnen und Autoren: Bernkopf D, Jalal K, Brückner M, Knaup KX, Gentzel M, Schambony A, Behrens J
Zeitschrift: Journal of Cell Biology
Jahr der Veröffentlichung: 2018
Band: 217
Heftnummer: 4
Seitenbereich: 1383-1394
ISSN: 0021-9525


Abstract

Mitochondrial abundance is dynamically regulated and was previously shown to be increased by Wnt/β-catenin signaling. Pgam5 is a mitochondrial phosphatase which is cleaved by the rhomboid protease presenilin-associated rhomboid-like protein (PARL) and released from membranes after mitochondrial stress. In this study, we show that Pgam5 interacts with the Wnt pathway component axin in the cytosol, blocks axin-mediated β-catenin degradation, and increases β-catenin levels and β-catenin-dependent transcription. Pgam5 stabilized β-catenin by inducing its dephosphorylation in an axin-dependent manner. Mitochondrial stress triggered by carbonyl cyanide m-chlorophenyl hydrazone (CCCP) treatment led to cytosolic release of endogenous Pgam5 and subsequent dephosphorylation of β-catenin, which was strongly diminished in Pgam5 and PARL knockout cells. Similarly, hypoxic stress generated cytosolic Pgam5 and led to stabilization of β-catenin, which was abolished by Pgam5 knockout. Cells stably expressing cytosolic Pgam5 exhibit elevated β-catenin levels and increased mitochondrial numbers. Our study reveals a novel mechanism by which damaged mitochondria might induce replenishment of the mitochondrial pool by cell-intrinsic activation of Wnt signaling via the Pgam5-β-catenin axis.


FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Behrens, Jürgen Prof. Dr.
Lehrstuhl für Experimentelle Medizin II (Molekulare Tumorforschung)
Bernkopf, Dominic Dr.
Lehrstuhl für Experimentelle Medizin II (Molekulare Tumorforschung)
Brückner, Martina
Lehrstuhl für Experimentelle Medizin II (Molekulare Tumorforschung)
Jalal, Kowcee
Lehrstuhl für Experimentelle Medizin II (Molekulare Tumorforschung)
Knaup, Karl Xaver
Medizinische Klinik 4 - Nephrologie und Hypertensiologie
Schambony, Alexandra Prof. Dr.
Lehrstuhl für Entwicklungsbiologie


Einrichtungen weiterer Autorinnen und Autoren

Max-Planck-Institut für molekulare Zellbiologie und Genetik / Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG)


Zitierweisen

APA:
Bernkopf, D., Jalal, K., Brückner, M., Knaup, K.X., Gentzel, M., Schambony, A., & Behrens, J. (2018). Pgam5 released from damaged mitochondria induces mitochondrial biogenesis via Wnt signaling. Journal of Cell Biology, 217(4), 1383-1394. https://dx.doi.org/10.1083/jcb.201708191

MLA:
Bernkopf, Dominic, et al. "Pgam5 released from damaged mitochondria induces mitochondrial biogenesis via Wnt signaling." Journal of Cell Biology 217.4 (2018): 1383-1394.

BibTeX: 

Zuletzt aktualisiert 2019-28-03 um 17:08